title: Fast detection of drug interaction in Mycobacterium tuberculosis by a checkerboard resazurin method.
abstract: Tuberculosis (TB) is a health public problem and a long combination therapy is necessary to treat patients. In recent years, some drugs, not routinely used in treatment of TB, have appeared as promising new anti-TB therapies in patients with resistance to classical drugs. The aim of this study was: (i) to evaluate a modified checkerboard assay, Resazurin drugs combination microtiter assay (REDCA) to detect drugs interaction in Mycobacterium tuberculosis; (ii) to evaluate the interaction between isoniazid (INH) or ethambutol (EMB) with levofloxacin (LEVO) in susceptible and resistant M. tuberculosis Brazilian clinical isolates. M. tuberculosis H37RV ATCC 27294 and 19 clinical isolates (10 resistant and 9 susceptible) were tested. The fractional inhibitory concentration index (FICI) ≤ 0.5 was considered synergistic. Synergism in M. tuberculosis H37RV and resistant M. tuberculosis Brazilian isolates was observed with EMB vs. LEVO. No synergism was observed with INH vs. LEVO by both assays. No statistical difference was observed by the two assays studied. REDCA showed to be a simple assay for detecting synergism between drugs in M. tuberculosis. The results with EMB vs. LEVO are promising and it can be a new option in future investigations of drugs interactions against M. tuberculosis with the view to reduce EMB adverse effects.
authors.affiliation: Postgraduate Program in Health Science, State University of Maringá, Paraná, Brazil; Laboratory of Medical Bacteriology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil. Electronic address: katianyrcf@gmail.com.
authors.forename: Katiany R
authors.initials: KR
authors.lastname: Caleffi-Ferracioli
authors.forename: Flaviane G
authors.initials: FG
authors.lastname: Maltempe
authors.forename: Vera Lúcia D
authors.initials: VL
authors.lastname: Siqueira
authors.forename: Rosilene F
authors.initials: RF
authors.lastname: Cardoso
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004977:Ethambutol / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007538:Isoniazid / Q000494:pharmacology; D064704:Levofloxacin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010078:Oxazines; D014376:Tuberculosis / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000382:microbiology; D014966:Xanthenes
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations; D007202:Indicators and Reagents; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin; D064704:Levofloxacin; D004977:Ethambutol; D007538:Isoniazid
keywords: Drugs; Mycobacterium tuberculosis; REDCA; Synergism